Epilepsy is a disorder that is prevalent in approximately 0.5-1% of the world's population (Sander, 2003, Curr Opin Neurol 16:165-170) and as many as 30% of these patients do not respond to currently available anti-epileptic drugs (AEDs) (Kwan and Brodie, 2000, N Engl J Med 342:314-319; Kwan and Sander, 2004, J Neurol Neurosurg Psychiatry 75:1376-1381). In patients with temporal lobe epilepsy, the most common form of epilepsy (Engel, J. J., and Pedley, T. A. (2008). Epilepsy: A Comprehensive Textbook 2nd ed. (Philadelphia: Lippincott Williams & Wilkins)), surgical resection of the epileptic focus can be a treatment option. However, controlled evaluations of surgical effectiveness indicate that seizures can be abolished in 60-80% of patients with TLE (Engel, 1996, N Engl J Med 334:647-652; Wiebe, et al., 2001, N Engl J Med 345:311-318), leaving a significant population of patients still affected by seizures. In addition, AEDs typically have adverse side effects since the mechanisms of action affect a wide variety of normal brain processes. Such short and long term side effects include psychomotor slowing, decreased cognition, sleepiness, gait disorders, osteoporosis, neuropathies, cerebellar atrophy, retinal damage, as well as liver, pancreas and bone marrow problems (Loyd et al., 2006, Pharmacoeconomics 23:1167-1181). Moreover, these drugs are not recommended for women of child bearing age, as they are known to be a potential cause of birth defects.
One of the most problematic and frustrating aspects of epilepsy, from the patient's perspective, is the uncertainty about if and when a seizure event will occur (Fisher et al., 2000, Epilepsy Res. 41:39-51). The earliest attempts to find seizure precursors that could be used to predict seizure onset used linear approaches to examine changes in the electroencephalograph (“EEG”) before seizure onset. Other approaches included power spectrum analysis of the EEG (Rogowski et al., 1981, Biological Cyberkinetics 42:9-15) or the occurrence rates of interictal spikes (Gotman and Koffler, 1989, Clin. Neurophysiol. 72:7-15), but these were not effective at predicting seizures. In the early 1990's nonlinear techniques began to be applied, including estimates of the largest Lyapunov exponent (Iasemidis et al., 1990, Brain Topography 2:187-201), correlation density (Martinerie et al., 1998, Nature Med. 4:1173-1176), and the dynamic similarity index (Quyen et al., 2000, Eur. J. Neurosci. 12:2124-2134). Therefore, to date, there remains a need for an effective method of detecting and predicting a seizure event. The present invention meets this need.